Project Summary Stress is associated with HIV risk behaviors, immune dysregulation, and among people living with HIV (PLWH) it has been associated with viral load and disease progression. The goal of this study is to better understand the mechanisms of stress and stress-related comorbidities and how they exacerbate HIV-related health disparities among HIV-infected Black men who have sex with men (BMSM). Studies in many parts of the US suggest that BMSM often live or spend much of their time in impoverished neighborhoods where physical and social disorders (e.g., physical decay, violence, discrimination) are clustered. These socio-structural factors can be conceptualized as chronic and acute stressors and may promote other stressors that lead to HIV-related outcomes. While much of the literature on minority stress has focused on major discriminatory events, this proposed study will examine microaggressions. We will comprehensively assess chronic, acute, and daily psychosocial stressors that are particularly relevant to MSM, especially BMSM. Moreover, we will use measures of hypothalamic?pituitary? adrenal (HPA) axis responses, sympathetic nervous system (SNS), and inflammatory biomarkers to identify specific stress pathways among HIV-infected BMSM and White MSM (WMSM) that can be targeted in future interventions. We aim to provide an extension of minority stress theory by utilizing intensive longitudinal protocols to assess daily discriminatory events and other stressors, and to explore the association with HIV-related behaviors and physiological outcomes. Built upon the evidence of feasibility and acceptability from our previous research, this aim will be accomplished by using ecological momentary assessment (EMA) of stressors and stress, Medication Event Monitoring System (MEMS), and home-based testing for cortisol. We propose a longitudinal study of 450 HIV-infected BMSM and WMSM who have common stress-related comorbidities (e.g., cardiovascular disease, depression, substance abuse) assessed at baseline, 6, 12, 18, and 24 months. Participants will provide 9 days of smartphone- based EMA and MEMS for ART medication adherence every 6 months for 24 months. Every 6 months, we will collect stress and immune function biomarkers.